Can Ovarian Stimulation Increase Endometrioma Volume?

Ovarian stimulation has been shown to increase endometrioma volume; however, this growth may not be clinically significant.

Key Points

Highlights:

• This study focuses on the relationship between endometrioma volume and ovarian stimulation. The authors hypothesize that ovarian stimulation will result in larger endometriomas.

Importance:

• Ovarian stimulation is often used for assisted reproduction techniques. It is essential for the patient and healthcare provider to know about all side effects, such as endometrioma growth, before recommending or committing to a procedure.

What’s done here?

• There were 25 participants in this study, all of whom had at least 1 endometrioma.
  • An endometrioma was defined as an ovarian cyst that had regular margins and ground glass echogenicity as viewed on a transvaginal ultrasound examination.
• In brief, the ovarian stimulation protocol consisted of:
  • There were two different Gonadotrophin-releasing hormones (GnRH) agonist protocols.
    • The long GnRH protocol consisted of daily subcutaneous injections of leuprolide acetate (0.5 mg) starting at the mid-luteal phase of the previous cycle till the day of ovulation trigger.
    • The GnRH protocol consisted of daily subcutaneous injections of cetrorelix acetate (0.25 mg) starting at the 6th day of ovarian stimulation and ends on the day of ovulation trigger.
  • Gonadotropin injections (150 – 450 IU) were administered on the 2nd or 3rd day of menstrual bleeding.
  • If 2 or more follicles attained a size of 18 mm in diameter, the patient was given recombinant HCG (250 g) and after 36 hours had to undergo transvaginal oocyte retrieval.
  • If the patient underwent embryo transfer, a Wallace or Cook catheter was used to transfer 1-2 embryos on the 3rd or 5th day
• The following procedure was used to assess the volume of the endometrioma:
  • Ovarian stimulation was analyzed using two and three-dimensional ultrasound with a Voluson E8 that utilized Sono-automated volume calculation (AVC) software.
  • Endometrioma volume was analyzed on two separate occasions: on the first day of gonadotropin injection and on the day of ovulation trigger. The software is used to calculate the volume.
• The data from this experiment was subject to statistical analysis.

Key results:

• Of the 25 participants with 28 endometriomas included in this study:
  • 9 were stimulated in a GnRH antagonist cycle.
  • 13 were stimulated in a long GnRH agonist protocol.
  • 3 were stimulated in an ultra-long GnRH agonist protocol.
• The mean duration of ovarian stimulation in participants was 10.3 days.
• The median total gonadotrophin dose administered in this study was 4500 IU/day.
• There was a median number of 4 metaphase-two oocytes, 5 cumulus-oocyte complexes, and 4 follicles wider than 14 mm.
• During oocyte retrieval, the researcher did not puncture any endometriomas.
• Medium endometrioma volume on the first day of gonadotropin injection was 22.2 ml.
• Medium endometrioma volume on the day of the ovarian trigger was 24.99 ml.
• 23 of the 28 endometriomas grew while the patient was undergoing ovarian stimulation. This growth was related to the cyst volume before stimulation. That being said, the average growth observed (3 ml) is statistically significant but may not be clinically significant.  

Limitations of the study:

• The participants were recruited from one institution in one area of the world. Thus, the results of the study may not apply to individuals from other regions of the world.

Lay Summary

Seyhan et al. recently published a paper titled “Do endometriomas grow during ovarian stimulation for assisted reproduction? A three-dimensional volume analysis before and after ovarian stimulation” in Reproductive BioMedicine Online. The authors initially believe that ovarian stimulation, often used in assisted reproduction techniques, can be linked to an increase in endometrioma volume.

The researchers studied 25 women and 28 endometriomas. Each woman had at least 1 endometrioma. The patients underwent ovarian stimulation where they could have been subject to one of 3 Gonadotrophin-releasing hormone (GnRH) agonist protocols: regular (9 participants), long (13), and ultra-long (3). Ovarian stimulation was then analyzed using a two and three-dimensional ultrasound with a Voluson E8 that utilized Sono-automated volume calculation (AVC) software. The software was used to calculate endometrioma volume on two separate occasions: the first day of gonadotropin injection and the day of ovulation trigger. The data from the experimental process was subject to statistical analysis.

The mean duration of ovarian stimulation was 10.3 days. The median total gonadotrophin dose administered was 4500 IU/day. There were no punctured endometriomas as a result of oocyte removal. The medium endometrioma volume on the first day of gonadotropin injection, defined as VI, was 22.2 ml, whereas the medium endometrioma volume on the day of ovarian trigger, defined as V2, was 24.99 ml. There were 23 endometriomas that grew during the process of ovarian stimulation. The researchers believe that this growth is correlated with cyst volume before stimulation. That being said, the authors of this publication state that the observed average endometrioma growth of 3 ml, while statistically significant, may not be clinically significant.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29203384